Prevalence and Predictors of Vascular Cognitive Impairment in Patients With CADASIL

Abstract

Background and objectives: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of stroke and early-onset dementia. We determined the prevalence of vascular cognitive impairment (VCI) in a group of patients with CADASIL and investigated which factors were associated with VCI risk, including clinical, genetic, and MRI parameters.

Methods: Cognition was assessed in patients with genetically confirmed CADASIL (n = 176) and healthy controls (n = 265) (mean [SD] age 50.95 [11.35] vs 52.37 [7.93] years) using the Brief Memory and Executive Test (BMET) and the Montreal Cognitive Assessment (MoCA). VCI was defined according to previously validated cutoffs. We determined the prevalence of VCI and its associations with clinical risk factors, mutation location (epidermal growth factor-like repeats [EGFr] 1-6 vs EGFr 7-34), and MRI markers of small vessel disease.

Results: VCI was more common in patients with CADASIL than in controls; 39.8 vs 10.2% on the BMET and 47.7% vs 19.6% on the MOCA. Patients with CADASIL had worse performance across all cognitive domains. A history of stroke was associated with VCI on the BMET (OR 2.12, 95% CI [1.05, 4.27] p = 0.04) and MoCA (OR 2.55 [1.21, 5.41] p = 0.01), after controlling for age and sex. There was no association of VCI with mutation site. Lacune count was the only MRI parameter independently associated with VCI on the BMET (OR: 1.63, 95% CI [1.10, 2.41], p = 0.014), after controlling for other MRI parameters. These associations persisted after controlling for education in the sensitivity analyses.

Discussion: VCI is present in almost half of the patients with CADASIL with a mean age of 50 years. Stroke and lacune count on MRI were both independent predictors of VCI on the BMET.

Figure 1. Z Scores of Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Patients Overall, With and Without Stroke and Controls on the Individual Brief Memory and Executive Test Tasks

Figure 2. Z Scores of Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Patients Overall, With and Without Stroke and Controls on the BMET Subscales and Total Brief Memory and Executive Test Score